Only a tiny fraction (~1%) of all microorganisms can be grown in the laboratory, so the potential of 99% of the world’s microorganisms has been locked away. Now, metagenomics techniques make it possible to sequence entire environmental samples at once, avoiding the need for laboratory culturing before DNA sequencing. This opens the doors to a treasure trove of genetic sequence data. But because of the very large volumes of data produced, analysis is the major bottleneck to exploiting metagenomic collections for enzyme discovery.

Biocatalysts Ltd have worked with The European Bioinformatics Institute (EMBL-EBI) to develop a novel, unique software platform for data analysis called MetXtra™, launched at Food Ingredients Europe 2017 in Frankfurt, Germany. MetXtra™ is a system for identifying completely novel enzymes rapidly from large metagenomic DNA sequence libraries. This allows food industry researchers, among others, to discover unique enzymes quickly and rationally for specific applications. Food enzymes are used to improve many food production processes, for example protein hydrolysis, carbohydrate modification, flavour generation and many more.

Biocatalysts Ltd coupled their proprietary metagenomic libraries with open datasets in EBI Metagenomics (https://www.ebi.ac.uk/metagenomics/), a public resource for metagenomics data developed at EMBL-EBI. Mining this data resulted in a collection of over 111 million unique protein sequences, which function in diverse environmental niches (e.g. hot/cold, acid/alkaline, saline). But analysing such a huge collection manually was not practical.

To solve the problem, Innovate UK supported a collaboration between Biocatalysts Ltd and EMBL-EBI – a publicly funded intergovernmental research institute and data provider – to develop new technology for searching and analysing very large datasets automatically. The new proprietary platform, MetXtra™, enables Biocatalysts to screen metagenomic libraries for enzymes in minutes, rather than days.

To refine the candidate enzyme list, MetXtra™ filters results through bespoke algorithms. These algorithms encompass customer specifications and requirements such as solubility, pH and temperature, so that the final set of candidate enzymes is targeted specifically to the researcher’s needs. This rational selection process ultimately gives fast, low-cost access to enzymes with a higher probability of being commercially successful.

Dr Andrew Ellis, Technical Director at Biocatalysts commented:“MetXtra™ is an extremely exciting new capability for Biocatalysts Ltd and its customers. The multidisciplinary team of software engineers, bioinformaticians, biologists and chemists have developed something truly unique. MetXtra™ adds a new dimension to our expanding enzyme development and manufacturing capability and we have already started to successfully apply it to identify novel and beneficial food enzymes.”

Dr Rob Finn, Team Leader at EMBL-EBI and Head of the EBI Metagenomics platform, commented:“EMBL-EBI provides foundational data resources to support innovation in all sectors. We are keen to support all life scientists in their quest to explore and apply knowledge in new ways. Our collaboration with Biocatalysts enabled us to calibrate our pipelines so we could better serve the biotech sector. Specifically, we produced new views of the data that are appropriate to enzyme-discovery biologists. It’s been amazing to see the pace at which Biocatalysts has produced real-world solutions from their integrated metagenomics dataset. We hope others will embrace the potential of ‘Nature’s protein engineering’, and use EBI Metagenomics to innovate.”